Introduction
Antimicrobials are essential for the treatment of bacterial infections
in humans and animals and have revolutionized human healthcare practices
worldwide. Penicillin, for instance, lowered mortality linked with
pneumococcal pneumonia from 20-40% to 5% and mortality from
pneumococcal bacteremia from 50-80% to 18-20% (Laxminarayan et al.
2016). Bacterial resistance to antimicrobials, however, quickly became a
substantial clinical problem threatening the advances of the prior
decades (Ventola, 2015) and posing a significant threat to public
health. When a microorganism that was susceptible to an antibiotic is no
longer sensitive due to the acquisition of resistance determinants,
antibiotics become less effective and treatment options are limited.
This acquired resistance phenotype contrasts with natural resistance
presented by several bacteria, which has existed for millions of years,
and is an evolutionary consequence of microbial competition in their
ecological niches (D’Costa et al., 2011). Bacteria acquire resistance
through mutations and horizontal gene transfer of resistance
determinants. Direct inactivation of antibiotics (e.g. , by
β-lactamases), modification (i.e. , mutation) of cellular targets
and modification of cell wall, are examples of resistance
strategies/mechanisms that microorganisms employ (Levy and Marshall,
2004). Mutation and mobilization of genes encoding resistance
mechanisms, as well as adaptive resistance phenotypes, are fostered by
the same factors that promote antibiotic usage, particularly prolonged,
cumulative, low-level exposure, including antibiotic overuse,
demographic changes associated with urbanization and poor sanitation,
discharge of antibiotic residues through environmental wasting and
biocide use in livestock production (Marshall and Levy, 2011;
Laxminarayan et al., 2013; Woolhouse et al., 2015). Still, antibiotic
consumption and overuse are considered the primary drivers of AMR (Klein
et al., 2018) and a substantial part of the resistance burden in humans
is attributable to antimicrobial use in livestock production, primarily
for disease prevention and growth promotion purposes (Marshall and Levy,
2011; Woolhouse et al., 2015). For example, antimicrobials used in
livestock are expected to account for circa 80% of the U.S.A.
annual antimicrobials consumption (Bartlett et al., 2013) and 73%
globally (Van Boeckel et al., 2019).
AMR is now recognized as a complex, multi-layered global problem, that
extends beyond national and animal borders, threatening human, animal
and environmental health (Queenan et al., 2016; Walsh, 2018; White and
Hughes, 2019). Various authors have strongly encouraged a holistic and
multidisciplinary “One Health” approach to tackle AMR, while stressing
out that the increasing incidence of AMR in humans and livestock has
been linked to the emergence of AMR in wildlife (Jones et al., 2008;
Wellington et al., 2013). Despite a large, and growing, literature on
AMR in the medical and veterinary settings, there is still a dearth of
research on the complex transmission dynamics of AMR in the
environmental and wild compartments (Allen et al., 2011), even though
the range, distribution and number of wild species (only birds
(Barrowclough et al., 2016) and mammals (Burgin et al., 2018)) is around
600 times higher than livestock (40 species and 4,500 breeds Barker
1999). Several studies have reported wildlife species as potentially
important reservoirs of resistant microorganisms and resistance genes
(Arnold et al., 2016; Vittecoq et al., 2016). For example,Escherichia coli isolates producing extended spectrum
beta-lactamases (ESBL) have been isolated from wild boar (Sus
scrofa ) in several European countries (Poeta et al., 2009; Krizman et
al., 2017; Bonardi et al., 2019), putting at stake the efficacy of
beta-lactam antibiotics (e.g. penicillin), which are amongst the
most important class of antimicrobial agents used in human and
veterinary medicine.
So, there is an urgent missing link, that upon revelation will
contribute to the understanding of the origins and roles of antibiotic
resistance genes in the gut microbiota of wildlife and the complex
transmission dynamics of the underlying determinants in the
environmental setting (Allen et al., 2010; Wellington et al.,2013). Howbeit, AMR is deemed as one of the major public health concerns
of the 21st century (Woolhouse and Farrar, 2014;
Laxminarayan et al., 2016), knowledge concerning AMR bacteria
circulating in wildlife is currently limited, although available
literature suggests that this wild compartment could provide important
insights into AMR emergence and persistence (Allen et al., 2010;
Wellington et al., 2013). Theoretically, wild animals are not treated
with antibiotics, but their association, both direct and indirect, with
humans, livestock, domestic animals or humanized-environments, their
ability to easily move across environmental gradients of humanization
(from pristine – natural – agroforestry – to highly humanized
scenarios), can enhance their contact with selective agents, with
commensals from humans and other species, as well as with resistant
bacteria. This contact is considered to promote adaptation mechanisms of
commensal bacteria and horizontal transfer of resistance genes within
the bacterial community of wildlife. Additionally, some of these species
(e.g. wild ungulates such as wild boar, among others) are
emerging as source of foodborne pathogens in humans due to the
manipulation and consumption of game meat (Dias et al., 2015, 2019;
Navarro-Gonzalez et al., 2018; Torres et al., 2019b). Altogether, AMR
research has to assume a multidisciplinary dimension crossing fields
such as microbiology, genomics, environmental science, ecology,
agriculture, pharmaceutical industry, synthetic biology, biotechnology
and health sciences (Torres et al., 2019a). Neglecting the dialog across
different disciplines will hamper our ability to detect, and thus
control, the increasing complexities of the factors involved in AMR
dynamics.
An analysis that could depict and explore the fact that AMR in wildlife
has hitherto received so little attention would be of value, not only to
academic researchers but to various stakeholders involved in the topic.
The analysis of research trends through bibliometric studies is
receiving considerable attention, as they provide valuable information
on scientific research and its progression in a specific field of
research (Nakagawa et al., 2019). Such analysis allows mapping the
structure and accumulation of scientific knowledge in specific fields,
allowing the assessment of the evolution of specific disciplines
(Zupic and Čater, 2015) by categorizing
descriptors such as citations, years, author affiliations, keywords,
countries, publication categories, among others
(McBurney and Novak, 2002). Previous
bibliometric studies on AMR were related to drug-resistance in specific
diseases and bacteria (Qin,
2000; Sweileh et al., 2016b, 2016a,
2017b, 2017c, 2017a), disease surveillance programs (Reaves et al.,
2017) as well as social impact (Frid-Nielsen et al., 2019).
This study exposes the gaps in the literature relating to the role of
wildlife as drivers for the spread of AMR bacteria, by (1) providing a
global overview of the spatial and temporal trends of reported
scientific knowledge on antimicrobial resistance in wildlife and (2)
identifying relevant research gaps both in terms of geographical
incidence and also in relation to the subtopics that should be
addressed. To deliver such information, peer-reviewed publications of
AMR in wildlife were retrieved from the Web of Science, systematized and
examined to illustrate the trends and evolutions on this topic.